Alopecia is the general term referring to any disease or condition involving hair loss. There are several different types of hair loss, the most common being androgenetic alopecia (AGA; see Sawaya, M. E. Seminars in Cutaneous Medicine and Surgery 17(4):276–283, 1998), alopecia areata (AA; see Fiedler & Alaiti, Dermatologic Clinics 14(4): 733–738, 1996, as well as drug-induced alopecia.
Androgenetic alopecia (AGA) is a patterned, progressive loss of an excessive amount of hair from the scalp. Significant AGA occurs in 50% of men by the age of fifty and 50% of women by the age of sixty. AGA is believed to be a result of both genetic predisposition and the presence of a sufficient level of circulating androgens. It is thought that the enzyme 5 alpha reductase present in dermal papilla cells converts testosterone to dihydrotestosterone (DHT). DHT binds to androgen receptors, also localized in the dermal papilla cells, triggering changes in the hair follicle that result in (1) shortening of the anagen or growth phase of the hair cycle and lengthening of the telogen or hair regeneraton stage, (2) development of a latent phase in the hair cycle following shedding of the telogen hair, and (3) follicular miniaturization that reduces the calibre of the anagen hairs produced. It is thought that differential expression of 5-alpha reductase and/or androgen receptors in various types of hair follicles accounts for patterned hair loss.
The current treatments for AGA include minoxidil (Rogaine™), an anti-hypertensive drug for which the mechanism of action in promoting hair growth is unknown. Minoxidil must be applied topically on a daily basis, and is therefore somewhat inconvenient to use. Another drug used in the treatment of AGA is finasteride (Propecia™), a selective inhibitor of the type 2 isoenzyme 5-alpha reductase. This treatment has minimal efficacy, requires daily administration and has some anti-androgenic side effects such as alteration of libido. Hair transplants are also performed on the scalp of patients with hair loss associated with AGA, but these are prohibitively expensive for many people, and often require multiple time-consuming sessions to complete.
Alopecia areata (AA) has been reported to account for 2% of new outpatients in dermatology clinics (Fiedler & Alaiti supra). AA is a nonscarring form of hair loss which occurs in humans and other species and is thought to be due to an inflammatory reaction caused by autoimmune response directed against the anagen stage hair follicle structure (McElwee et al. Pathobiology 66(2): 90–107, 1998).
A number of therapeutic modalities have been tested for the treatment of AA, with variable results ranging from no effect to partial or full hair regrowth. In some cases chronic maintenance treatment is required. Major drawbacks of these treatments are side effects, which can be local or systemic in nature. Fiedler & Alaiti (supra) and Shapiro (Dermatological Clinics 11(1): 35–46, 1993) have reviewed the various treatments available for AA, including steroids (topical, intralesional and systemic), minoxidil, anthralin, photochemotherapy, cyclosporin A and other agents, as well as combination treatments.
Photochemotherapy therapy for AA using psoralen and high energy UVA (PUVA) treatment has met with very limited success and its effectiveness for AA is in doubt (Lebwohl, M. Lancet 349:222–223, 1997). Side effects of PUVA treatment such as nausea, pigmentary changes, risk of skin cancer formation, and cataracts have been reported (Fiedler & Alaiti, supra). Antioxidants have been used to ameliorate the side-effects of PUVA therapy (Ptapenko & Kyagova, Membr. Cell Biol. 12(2): 269–278, 1998). The use of 2% khellin, a compound with a chemical structure that resembles psoralen, and UVA for alopecia areata was found to be successful in 5 of the 10 patients tested (Orasa et al. Int. J. Dermatol. 32(9): 690, 1993). Since Khellin did not cause phototoxicity, the authors have suggested its use as an alternative to psoralen.
Hematoporphyrin and high energy UVA has been used in a very limited study by Monfrcola et al. (Photodermatology 4:305–306, 1987). Two patients were treated with topical hematoporphyrin (0.5%, HP) and UVA irradiation with three times a week for eight weeks. In the first week of treatment there was significant erythema and mild scaling followed by hyperpigmentation in the HP treated sites. Side effects included unpleasant reddish skin coloration for several hours and sometimes burning sensations during the irradiation phase. The authors point out that severe phototoxic reactions could occur with the use of HP concentrations greater than 1%. They also state that more work is needed before this approach can be subject to routine clinical use.
Photodynamic therapy (PDT) has been utilized for the removal of unwanted hair in human subjects. Briefly the treatment involves a topical application of a photosensitizer on a selected area of the skin, a period for absorption of the photosensitizer, followed by a pulse or continuous irradiation or vibration of the area. The process involves inactivating or destroying the hair follicles or destroying the tissue feeding the hair follicles (see U.S. Pat. Nos. 5,669,916; 5,871,480; WO 97/32046).
Photodynamic therapy is a minimally invasive two-step medical procedure that uses light-activated drugs called photosensitizers to treat a range of diseases involving rapid cell growth, such as cancerous tumors or abnormal blood vessels. First, a photosensitizer is administered and, once it has permeated the target tissue of interest, the photosensitizer is then activated by exposure to a pre-calculated dose of light at a particular wavelength. Once activated, the drug converts oxygen found in the cells into highly energized singlet oxygen. Singlet oxygen can react with subcellular components such as proteins and lipids, which disrupts normal cellular function and results in killing the cells. Lasers and fiber optics are used to deliver light.
There continues to be a need for a simple, rapid, and relatively side effect free method for stimulating and/or restoring hair growth in areas of hair loss.
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